RepState: DNA Repair State Machines

The Doctoral Network RepState aims to train a new generation of innovative scientists in biochemistry and biophysics to address central questions in biology concerning the mode of action of critical DNA Repair proteins that act as state machines.

RepState consists of a highly collaborative consortium consisting of 11 participants coming from academia, industry and the creative sector, representing the natural sciences as well as the social sciences.

Participating laboratories in RepState are part of established research schools within renowned research organizations and universities. This environment of excellence offers a multidisciplinary PhD program to 13 young researchers, through training in the fundamental chemical and physical principles that underlie biology and human health. In addition, training will focus on method development using technology and experience provided by the academic participants as well as by the two small technology-driven companies.

Training incorporates a local program, rotations within partner laboratories, exposure to the non-academic sector and annual meetings. Fellows will follow scientific workshops, courses in transferable skills and career development, and will disseminate and communicate their projects to a diverse audience in close collaboration with the creative sector. The RepState fellows will form a new generation of mature and innovative European scientists with a thorough understanding of fundamental quantitative principles underlying biology, with experience in technique development, career perspectives in multiple sectors and an understanding of the importance of the role of fundamental science for society and human health. 

RepState is training a new generation of interdisciplinary biochemists and biophysicists to appreciate how new technologies can be combined to generate novel insights and how the fundamental physical and chemical properties of molecules relate to their behavior within a living cell.

The researchers will also learn to create and benchmark highly pure and homogeneous reagents and operate cutting-edge technologies. Furthermore, the students will explore new way and means to communicate their results and the importance of fundamental research in general to society. This combination of expertise is not provided for by existing educational programs. Our network would therefore create a unique training environment in skills and experiences that are both highly valued and in short supply within the expanding biosciences sector.

Objectives – RepState aims to create a Doctoral Training Network focused on unraveling the molecular details of the mode of action of DNA Repair State Machines that are crucial for maintaining genome stability. RepState will do so by developing new technologies with high temporal and spatial resolution to study structure and function of DNA Repair State Machines for the two crucial, connected DNA repair pathways MMR and NER. To understand how the state machines coordinate reaction sub-steps, RepState has formulated five research objectives that reflect successive reaction steps and their corresponding state machines in the MMR, NER and TC-NER pathways (Fig. 1). 

  1. Uncover the mechanism of activation of lesion recognition state machines.
  2. Dissect how this activation regulates multiple downstream actions on DNA.
  3. Decipher how DNA incision is activated.
  4. Decipher how DNA unwinding is activated.
  5. Unravel how the coordinated function of multiple state machines results in efficient DNA repair.
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